DOCK1

Chr 10

dedicator of cytokinesis 1

Also known as: DOCK180, ced5

NCBI Gene: 1793ENSG00000150760UniProt: Q14185OMIM: 601403

This protein functions as a guanine nucleotide exchange factor that activates Rac GTPases, regulating cytoskeletal rearrangements essential for phagocytosis and cell migration. Mutations cause autosomal recessive combined immunodeficiency characterized by severe infections due to defective phagocytosis and impaired immune cell function. The gene is highly constrained against loss-of-function variants (LOEUF 0.341), reflecting its critical role in immune system development and function.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.34
Clinical Summary— DOCK1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.
📋
ClinVar Variants
66 unique Pathogenic / Likely Pathogenic· 258 VUS of 405 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.34LOEUF
pLI 0.007
Z-score 7.49
OE 0.25 (0.18–0.34)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.41Z-score
OE missense 0.79 (0.74–0.83)
808 obs / 1025.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.25 (0.18–0.34)
0≤0.351.4
Missense OE0.79 (0.74–0.83)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 29 / 116.1Missense obs/exp: 808 / 1025.4Syn Z: 0.02
DN
0.6841th %ile
GOF
0.6735th %ile
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

405 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic2
VUS258
Likely Benign12
Conflicting1
64
Pathogenic
2
Likely Pathogenic
258
VUS
12
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
64
0
64
Likely Pathogenic
1
0
1
0
2
VUS
0
234
24
0
258
Likely Benign
0
9
1
2
12
Benign
0
0
0
0
0
Conflicting
—1
Total1243902337

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DOCK1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients